This invention relates to an improved tableted blood plasma microconcentrated thromboplastin coagulation reagent and a method for making it.
The invention is an improvement over the concept of preparing tableted blood plasma microconcentrated coagulation reagents generally. While methods for preparing blood plasma coagulation reagents have been known, the preparation of the reagents in tableted form is a recent innovation. Diagnostic or monitoring coagulation reagents are not amenable to manufacture using standard routes of biochemistry or automated production line techniques for producing tablets. Coagulation materials are extremely sensitive to degradation or alteration through improper processing and storage. Further, by their very nature, starting materials for coagulation reagents are frequently not at the same level of chemical activity, re-activity, purity, and so on. This means that every process step has to be customized depending on the starting materials used in each case.
Even with tailoring of the starting materials to safeguard against uneven activity, reactivity, purity, and the like, additional precautions must be taken to prevent contamination and deactivation of the active materials. Carriers, disintegrating agents, fillers, binders, and other materials commonly used in preparing tablets can be the source of such contamination or deactivation. Consequently, the technology involved in tableting coagulation reagents had to depart significantly from pharmaceutical or therapeutic utilities which employ a very large percentage of inert materials in every capsule or tablet.
Taking every precaution and exercising the highest degree of care, one can still encounter difficulties in tableting diagnostic coagulation reagents. One problem that has arisen in the tableted thromboplastin coagulation reagent appears to derive from a possible incompatibility between calcium and thromboplastin, both of which are critical to the performance of the coagulation test.
In preparing tableted thromboplastin coagulation reagents, problems arose in metering granules of the components to achieve accurate ratios of calcium and thromboplastin. Beyond that, and apparently because of the incompatibility of the two materials, some difficulty has been experienced in producing consistently homogeneous tablets at commercially acceptable yields, even from a homogeneous mixture of thromboplastin and a calcium salt. Inhomogeniety could sometimes be observed from tablet to tablet as well as within a select tablet. The combined components did not maintain their respective ratios consistently enough during the tableting operation to justify full-scale commercialization.
Another problem that has been encountered derives from the fact that calcium salts such as calcium chloride act as desiccants. Even though the calcium chloride is imprisoned in a tablet and even though the tablet is encapsulated in air tight packaging, the calcium salt can absorb moisture into the tablet. Moisture causes aggregation of thromboplastin with calcium as well as with other colloidal thromboplastin particles. As a result, the thromboplastin aggregates or agglomerates fall out of solution and do not participate as required in the test procedure.